We have developed several simple mathematical models of human body composition change that help elucidate the factors that determine the proportion of body fat versus lean mass change with weight loss or weight gain. These simple models have been used to analyze data from several published weight loss studies and allowed us to quantitatively link the physiological properties of fuel utilization to the long-term regulation of body composition. We have also used our simple models to delineate the limited applicability one of the most pervasive weight loss rules: that a cumulative energy deficit of 3500 kcal is required to produce one pound of weight loss. [unreadable] [unreadable] We also discovered simple equation that explains a wide variety of data on the changes of belly fat, called visceral adipose tissue, in relationship to the overall body fat mass. Visceral adipose tissue is believed to be particularly dangerous because it is highly correlated with cardiovascular and metabolic risk factors. A large number of studies have investigated whether diet interventions, exercise interventions, or even bariatric surgery can preferentially target the reduction of belly fat. However, our analysis of these data showed that changes of visceral adipose tissue mass do not depend on the type of weight loss intervention. Rather, a single equation shows that changes of visceral adipose tissue are primarily determined by overall body fat changes as well as the initial ratio of visceral to total body fat. Other predictions of the simple model relating visceral to subcutaneous fat have been confirmed by independent investigators.[unreadable] [unreadable] Finally, we continue to develop a complex model of human macronutrient metabolism and have conducted several validation studies using a variety of published data on the metabolic responses to overfeeding, underfeeding, and isocaloric changes in dietary macronutrients. The model is beginning to be deployed as a clinical research tool in collaboration with NIH clinical investigators to help design prospective studies as well as plan and track clinical weight management programs.